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A Dick

Publications and source records attributed to A Dick.

At least 37 records · Page 2Linked to original sources
PubMed1999

The smad5 mutation somitabun blocks Bmp2b signaling during early dorsoventral patterning of the zebrafish embryo.

Signaling by members of the TGFbeta superfamily is thought to be transduced by Smad proteins. Here, we describe a zebrafish mutant in smad5, designated somitabun (sbn). The dominant maternal and zygotic effect of the sbntc24 mutation is caused by a change in a single amino acid in the L3 loop of Smad5 protein which transforms Smad5 into an antimorphic version, inhibiting wild-type Smad5 and related Smad proteins. sbn mutant embryos are strongly dorsalized, similarly to mutants in Bmp2b, its putative upstream signal. Double mutant analyses and RNA injection experiments show that sbn and bmp2b interact and that sbn acts downstream of Bmp2b signaling to mediate Bmp2b autoregulation during early dorsoventral (D-V) pattern formation. Comparison of early marker gene expression patterns, chimera analyses and rescue experiments involving temporally controlled misexpression of bmp or smad in mutant embryos reveal three phases of D-V patterning: an early sbn- and bmp2b-independent phase when a coarse initial D-V pattern is set up, an intermediate sbn- and bmp2b-dependent phase during which the putative morphogenetic Bmp2/4 gradient is established, and a later sbn-independent phase during gastrulation when the Bmp2/4 gradient is interpreted and cell fates are specified.

Amino Acid Sequence↗
PubMed1999

Lipopeptides as dimerization inhibitors of HIV-1 protease.

In AIDS therapy, attempts have been made to inhibit the virus-encoded enzymes, e.g. HIV-1 protease, using active site-directed inhibitors. This approach is questionable, however, due to virus mutations and the high toxicity of the drugs. An alternative method to inhibit the dimeric HIV protease is the targeting of the interface region of the protease subunits in order to prevent subunit dimerization and enzyme activity. This approach should be less prone to inactivation by mutation. A list of improved 'dimerization inhibitors' of HIV-1 protease is presented. The main structural features are a short 'interface' peptide segment, including non-natural amino acids, and an aliphatic N-terminal blocking group. The high inhibitory power of some of the lipopeptides [e.g. palmitoyl-Tyr-Glu-Leu-OH, palmitoyl-Tyr-Glu-(L-thyronine)-OH, palmitoyl-Tyr-Glu-(L-biphenyl-alanine)-OH] with low nanomolar Ki values in the enzyme test suggests that mimetics with good bio-availability can be derived for AIDS therapy.

Amino Acid Sequence↗
PubMed1998

Expression of Smad1 and Smad2 during embryogenesis suggests a role in organ development.

Smad proteins are intracellular signalling molecules and putative transcription factors that transduce signals elicited by members of the transforming growth factor beta (TGF-beta) superfamily. By comparing the expression of Smad1 and Smad2 during embryonic development, we show that mRNAs of both Smad isoforms are present in a variety of tissues. The major sites of expression of both Smads can be correlated with the expression domains of several members of the TGF-beta superfamily. Our expression data suggest that Smad proteins are involved in organ development, particularly that of organs arising from mesenchymal-epithelial interactions. A second site of strong expression is the central nervous system. Transcriptional control mediated by Smad1 and Smad2, therefore, may exert an important function in differentiation processes of embryonic development that are controlled by ligands of the TGF-beta superfamily.

Animals↗
PubMed1998

Normalized activated protein C ratio itself not associated with increased risk of venous thromboembolism.

Recently, discussions focused on the question whether acquired activated (APC) resistance is a clue to the observed association between venous thromboembolism (VTE) risk and oral contraceptive (OC) use, especially with the so-called third-generation OC. The objective of our study was to check the validity of acquired APC resistance regarding VTE risk in a case-control study. Sixty-seven women with confirmed VTE diagnosis (n = 67) were consecutively ascertained in primary health care settings, interviewed and blood samples taken (at the earliest 6 months after VTE). Cases were age-matched to 290 population controls. Acquired APC resistance was measured as normalized APC ratio (APCRN). The effect of APC on tissue factor initiated thrombin generation was measured in plasma using alpha 2-macroglobulin attached thrombin activity as an endpoint. Higher risk (odds) ratio with 95% CI) of VTE for carriers of heterozygote Factor V Leiden mutation was confirmed [OR = 2.72 (CI:1.51-4.92)]. However, there is no association between VTE and the level of APCRN OR 0.65 (CI:0.35-1.22). We conclude that acquired APC resistance, measured with a tissue factor initiated test, is unlikely to have a direct association to the clinical outcome of venous thromboembolism.

Adolescent↗
PubMed1998

Changes in the zymogenic cell populations of the abomasa of sheep infected with Haemonchus contortus.

The effects of dietary urea supplementation and of a 10-week trickle infection regime, simulating chronic exposure to Haemonchus contortus, on the zymogenic population of the abomasa of Hampshire Down lambs was examined. At necropsy a variety of parameters including plasma pepsinogen concentration, the wet weights of abomasal fundic mucosal pieces and the amounts of pepsinogen contained in them, were assessed. Tissue pepsinogen concentration was measured as the total, acid-stable proteolytic activity present in mucosal homogenates, as well as immunohistochemically. The immunohistochemical findings were quantified using computer-aided image analysis. Elevation of plasma pepsinogen concentrations in infected animals was of borderline significance (P = 0.06). The fundic mucosae of infected animals were heavier (P < 0.02) than those of control animals, but there was no overall change in the pepsinogen content of tissues. Immunohistochemistry revealed that infected animals had increased numbers of zymogenic cells, due to mucous cell hyperplasia and the adaptation of cells to produce both mucins and pepsinogen. The pepsinogen content of chief cells, the major source of pepsinogen in uninfected animals, was reduced in infected lambs. Image analysis confirmed that at a mid-point of the mucosa of infected animals there was increased pepsinogen-specific immunoreactivity that corresponded with areas of mucosal hyperplasia. Mucous cell hyperplasia might therefore allow the maintenance of pepsinogen secretion in infected animals even if chief cell output is reduced.

Abomasum↗
PubMed1998

Resistance to activated protein C in women using oral contraceptives.

Resistance to activated protein C (APC resistance) is an important and common risk factor for deep vein thrombosis. The majority of patients with APC resistance carry a mutation on the factor V gene at nucleotide position 1691 (G/A), called factor V Leiden mutation. Besides the factor V Leiden mutation several acquired risk factors like lupus anticoagulant, elevated levels of acute phase proteins (increased plasma levels of factor VIII and fibrinogen), pregnancy, or the use of oral contraceptives are known to induce APC resistance in plasma. We studied the effect of oral contraceptives (OC) on hemostasis variables known to be risk factors for venous thromboembolism, especially looking for acquired APC resistance and the plasmatic factors of the protein C system. We studied 821 women, who were randomly selected and enrolled in the BATER- cohort study (Bavarian Thromboembolic Risk Study), which was carried out in Bavaria (Germany) from 1996 to 1997. Current use of any OC type compared with noncurrent use showed a significantly impaired response to APC. There was no difference in APC response among women currently using OCs of different generations. Coagulation factor VIII was the only factor of the protein C pathway that was not altered under OC use. All other plasmatic factors of the protein C system changed in the expected range as described before. On the other hand, coagulation factor VIII was the only factor of the protein C system which negatively correlated with the APC response in the assays applied. Thus, APC resistance is significantly lower in OC users than in nonusers but cannot be attributed to increased factor VIII levels. Whether a decreased response to APC in OC users is of clinical relevance has to be proven in further studies.

Activated Protein C Resistance↗
PubMed1998

Thrombolysis of mural thrombus by ultrasound: an experimental in vitro study.

RATIONALE AND OBJECTIVES: The authors perform an in vitro evaluation of the thrombus fragmentation to determine the efficacy and degree of downstream clot fragment embolization that occurs during transcatheter ultrasound treatment of fibrin-rich mural thrombus in a peripheral venous flow model with variable diameter tubing. METHODS: The authors used a 22.5-kHz prototype intravascular ultrasound device with a flexible 0.8-mm (.032-inch) titanium wire probe encased in a 7-French teflon guide catheter, at the tip of which is a 2-mm ball. In 50 silicone tube segments (inner diameter 3, 5, 7, 9, and 11 mm; n = 10 each), firmly adherent mural thrombus was produced using bovine blood in a modification of the Chandler's loop technique. Ultrasound energy (30-36 watts/cm), maximal longitudinal catheter tip amplitude 70 m) was applied to the thrombus while a continuous flow of water was maintained in the closed loop system. Clot fragment emboli were trapped in "downstream" polyethylene filters. RESULTS: The mean rate of thrombus removal ranged from 99% +/- 0.3% in the 3-mm segments to 76% +/- 6% in the 11-mm segments. The average weight of the fragments that embolized "downstream" and were trapped in the filters, expressed as a percentage of the initial clot weight, was 11% in the 3-mm segment, 14% in the 5-mm segment, 30% in the 7-mm segment, 29% in the 9-mm segment, and 28% in the 11-mm segments. The majority of the embolized fragments appear to be larger than 1 mm. CONCLUSIONS: In this in vitro venous flow model a lack of catheter steerability was the major obstacle to complete thrombus fragmentation in vessel calibers larger than two times the tip diameter. The rate of embolism and the amount of remaining thrombus that could not be removed from the vessel were higher in the larger vessels.

Animals↗
PubMed1998

Declotting of embolized temporary vena cava filter by ultrasound and the Angiojet: comparative experimental in vitro studies.

RATIONALE AND OBJECTIVES: The authors perform an in vitro evaluation of the thrombolytic efficacy and the amount of "downstream" embolization induced by two new mechanical thrombectomy devices when applied to clots trapped in a temporary vena cava filter. METHODS: The first device used was a 22.5-kHz prototype intravascular ultrasound device with a flexible 0.8-mm (.032-inch) titanium 2-mm ball-tipped wire probe ensheathed in a 7-French teflon guide catheter. The device was inserted through a 10-French steering catheter. Under fluoroscopic control, ultrasound energy (26 +/- 4 watts/cm2, maximal longitudinal catheter tip amplitude 54 microm) was applied to 10 Ultravist-filled porcine thrombi (mean, 3500 mg). The second device, the Angiojet catheter, was applied to five Ultravist-filled porcine thrombi (mean, 3640 mg). The thrombi were treated while trapped in a temporary Günther vena cava filter (Cook Europe, Bjaverskov, Denmark) mounted in a vena cava flow model. The resultant "downstream" emboli were trapped in two tandem filters of decreasing pore size and weighed. RESULTS: Mean thrombus dissolution rate was 53% +/- 22% standard deviation (SD) for the ultrasound device (n = 10) and 63 % +/- 8% SD for the Angiojet (n = 5) (difference statistically significant at P = 0.03). For the ultrasound device, the mean embolic particle weight caught by the filters with mesh widths of 1 mm and 0.1 mm was 42% +/- 14% SD and 4% +/- 2% SD, respectively, of the initial thrombus weight. For the Angiojet, the respective numbers were 35% +/- 16% SD and 3% +/- 1% SD. Mean treatment time was 216 +/- 45 seconds SD for the ultrasound device and 153 +/- 21 seconds SD for the Angiojet. CONCLUSIONS: The thrombolytic efficacy of the Angiojet was significantly greater and the treatment time was significantly shorter than that of the ultrasound device. Both systems had a high embolization rate.

Animals↗
PubMed1998

[CIPA (Comprehensive Individualized Process Analysis)--a method for combining quantitative and qualitative individual case analysis].

The main question of psychotherapy research nowadays is how psychotherapy works. Hence, interest focuses mainly on the process of psychotherapy. General change mechanisms as well as the therapeutic interaction are in the center of research interest. On the basis of process outcome findings (Orlinsky, Grawe, Parks 1994) and the schema theory of Grawe (1987) we developed a research instrument allowing the analysis of therapies from a theoretically and quantitative approaches. The research instrument (CIPA-Comprehensive Individualized Process Analysis) consist of three parts: The scales of the first part assess the general working mechanisms and the therapeutic relationship. The second part allows a rating of the patient's interactions inside and outside the therapy. In the third part the individual schemata are rated. The instrument and the research strategy are being illustrated by means of a selected therapy recorded completely on video tape. The results are interpreted on the basis of the individual schema structure as well as the therapy outcome. The possibility offered by the new instrument to combine quantitative and qualitative research strategies is discussed.

Adult↗
PubMed1997

Direct administration of charcoal into the lung and pleural cavity.

We report the inadvertent administration of activated charcoal in water into the right lung and pleural cavity of a 51-year-old man being treated for a salicylate overdose. A mild chemical pneumonitis developed, as did a sterile empyema. Charcoal-stained fluid drained through a thoracostomy tube for 8 weeks. The patient was discharged in good condition but died 4 days later after taking another overdose. Direct administration of charcoal into the lungs is best prevented by radiographic confirmation of the location of the tube. Charcoal in water may cause less severe pulmonary injury than charcoal in sorbitol.

Aspirin↗
PubMed1997

[Color-coded duplex ultrasonography of the orbit in central vein thrombosis].

PURPOSE: To evaluate the haemodynamic findings of orbital vessels in patients with central retinal vein occlusion by colour coded duplex sonography. METHODS: In 24 patients suffering from central retinal vein occlusion, confirmed by ophthalmoscopy and fluorescence angiography, colour-coded duplex sonography of central retinal vein, central retinal artery, posterior ciliary arteries and ophthalmic artery of the affected, and the unaffected contralateral eye, was performed and compared to a control group (150 healthy subjects). RESULTS: In eyes with central retinal vein occlusion, the maximum velocity of the central retinal vein was on average 4.55 cm/s (+/-2.37 cm/s) and, as compared with the unaffected eye (mean: 6.56 +/- 1.47 cm/s) and the control group (5.97 +/- 2.37 cm/s), reduced significantly. In the affected eyes, the end diastolic velocity of the central retinal artery was reduced and the pulsatility index was increased significantly, compared with the unaffected eyes and the control group. Compared with the control group, the peak systolic and end diastolic velocities of the ophthalmic artery were significantly reduced. CONCLUSION: In conclusion, the findings assessed by colour-coded duplex sonography show a flow reduction in the central retinal vein and an increased arterial flow resistance in the retinal layer. There is good correlation with the angiographic results. Moreover, flow reductions in the ophthalmic artery, which are not seen in ophthalmological examinations, can be detected by this new examination technique.

Adult↗
PubMed1996

[MRT of experimental liver abscesses: a comparison of a new blood pool contrast medium with gadolinium-DTPA in animal experiments].

PURPOSE: In an experimental pyogenic liver abscess model, the signal intensities were compared intraindividually and interindividually after the application of a new blood pool contrast agent, 24-gadolinium-DTPA (diethylenetriamine-pentaacetic acid) cascade polymer, and after the application of gadopentetate dimeglumine. METHODS: In 20 rabbits with experimentally induced liver abscesses, the relative signal intensities of the liver, abscess centre, abscess wall and portal vein were assessed before and between 30 seconds and 60 minutes after injection of a 25 mumol/kg dose of gadolinium polymer and of 100 mumol/kg of gadolinium-DTPA, respectively. Measurements were performed at 1.5 Tesla, using a head coil and a Flash-2-D sequence. RESULTS: The interindividual comparison (unpaired T-test, p < 0.05) yielded significant differences of the relative signal intensities of the abscess centre (at any time point after contrast-media application), abscess wall (between 15 and 60 minutes after contrast media application), and portal vein (between 30 seconds and 7.5 minutes after contrast media application). The interindividual comparison showed a significantly higher abscess centre-liver contrast (between 30 seconds and 12.5 minutes after contrast media application) and a significantly higher abscess wall-centre contrast (between two and 7.5 minutes after contrast media application) after the application of gadolinium polymer compared with gadopentetate dimeglumine. CONCLUSION: In this animal model, the higher abscess centre-liver contrast after the application of gadolinium polymer was the basis for a better and prolonged visibility of the abscesses, as compared with images acquired after injection of gadopentetate dimeglumine.

Animals↗
PubMed1996

Computed tomography of experimental liver abscesses using a new liposomal contrast agent.

RATIONALE AND OBJECTIVES: Evaluation of computed tomographic enhancement characteristics of a new liposomal contrast agent (liposomal iodixanol [LI]) in a pyogenic liver abscess model in 17 rabbits. METHODS: Eight to 14 days after abscess induction (Escherichia coli), density-time curves were calculated for regions of interest in liver, abscess wall and center, spleen, portal vein, abdominal aorta, inferior vena cava, and kidney. Images were obtained every minute between 1 and 10 minutes, every 5 minutes between 15 and 60 minutes, and 75 minutes after 200 mg/kg LI application (group A: 7 rabbits) and after 600 mg/kg iopentol application (group B: 10 rabbits), and 90, 105, and 120 minutes after LI. RESULTS: The abscess wall-liver contrast after LI lasted from 10 to more than 120 minutes with a maximum of 30 delta Hounsfield Units (HU) at 45 minutes. For iopentol, the abscess wall-liver contrast lasted from 2 to 7 minutes with a maximum of 8 delta HU at 5 minutes. The abscess wall-center contrast after LI lasted from 1 to more than 120 minutes with a maximum of 112 delta HU at 40 minutes. For iopentol, the abscess wall-center contrast lasted from 1 to 75 minutes with a maximum of 79 delta HU at 1 minute. The liver-portal vein contrast after LI lasted from 1 to more than 120 minutes with a maximum of 100 delta HU at 20 minutes. For iopentol, the liver-portal vein contrast lasted from 1 to 8 minutes with a maximum of 38 delta HU at 2 minutes. An abscess wall was detected in a higher percentage of the LI images (86% LI, 56% iopentol), and images in the LI group correlated better with histopathology. CONCLUSIONS: The diagnostic value of LI exceeds that of iopentol in terms of overall abscess contrast and duration of the diagnostic interval. The higher hepatic vessel contrast allows better abscess localization.

Animals↗